1. Field of the Invention
The present invention pertains to an apparatus and method to enable minimally invasive trans-cutaneous measurements of the fluorescence of an implanted element without reagent consumption and not requiring invasive sampling. The procedure is completely non-invasive after one implant. The monitoring apparatus displays the quantity of a selected substance present in the skin and stores the data in memory. The stored information can be transmitted via modem, or antenna, to a master station for diagnostic purposes or clinical evaluation. The use of this method and apparatus improves control of blood monitoring, and therefore, enhances long-term disease management with fewer complications.
2. Description of the Prior Art
Instruments capable of continuously indicating the chemical composition of blood have proved to be useful in regulating operative and postoperative managements of patients, in teaching and research. At first, such instruments were used with sensors mounted directly in the extracorporeal blood circuit that is used for perfusion of open-heart surgery patients. Later, continuous monitoring of both machine and patients was conducted by means of continuous withdrawal of blood pumped into external cuvettes equipped with appropriate sensors, or by use of implantation of arterial catheters.
Other techniques have been employed for measuring biological substances in the blood. For instance, ethanol is currently measured in blood, either directly or by a breath sampling, by classical chemical, gas chromatographic and enzyme methods. One of the alcohol enzyme methods depends upon the polarographic measurement of hydrogen peroxide, while others depend upon the consumption of oxygen.
The continuous monitoring of blood oxygen by a heated electrode positioned on hyperemic skin has been accomplished. Substances such as halogenated organic compounds, particularly fluorinated compounds, have also been found to diffuse through the skin and have been measured.
Other methods for cutaneously measuring substances in the blood include contacting the substrate through the skin of a mammal with an enzyme selective for the substrate being analyzed, then reacting the substrate with the enzyme and directly detecting a condition of the skin as a measure of the amount of substrate.
The following are representative of the prior art systems available:
Wider et al., U.S. Pat. No. 5,184,618 discloses a system for invasively measuring blood gas parameters, such as pH, pO.sub.2 or pCO.sub.2, or for measuring other parameters influencing the time constant of the excited state of a fluorescent dye and a correlation between the respective values of the blood gas parameter and the associated values of the time constant of the fluorescent measuring probe.
Murray Jr. et al., U.S. Pat. No. 4,752,115, discloses a device for sensing oxygen, particularly for use in medical applications. The device includes an optical waveguide and an oxygen sensing medium disposed on the waveguide. The sensing medium fluoresces in response to light from a light source such that the intensity of fluorescence is dependent on the partial pressure of oxygen in the environment. The sensing medium includes an oxygen sensitive fluorescent dye in a matrix consisting of a plasticized polymer.
Lefkowitz et al., U.S. Pat. No. 4,994,396, discloses a sensor and a method for determining the concentration or the partial pressure of oxygen comprising (a) means for transmitting and collecting light to and from a light modifying medium; and (b) a light modifying medium containing a luminescent dye dispersed in or upon a matrix and the dye is accessible to oxygen, wherein said luminescent dye contains a hexanuclear core of molybdenum, tungsten or mixtures thereof having coordination sites, wherein each coordination site is occupied by a ligand.
Khalil et al., U.S. Pat. No. 5,043,286 discloses methods of and luminescent substances for measuring oxygen concentration of a test fluid. A test fluid is contacted with a plastic film containing a luminescent substance, the luminescent emission intensity of which is quenched in the presence of oxygen. The film is subjected to irradiation by light that is strongly absorbed by the luminescent substance, and a measure of the time dependence of luminescent emission intensity I(t) is obtained. Three modes of measuring quenching, and thus the oxygen concentration, from I(t) are described.
Khalil et al., U.S. Pat. No. 5,284,159, discloses a method for converting a value for the partial pressure of oxygen (pO.sub.2) in blood at a measurement temperature to a corresponding value at a reference temperature (37.degree. C.). A value for pO.sub.2 is determined by measurements made in a patient's blood stream using a phosphorescent compound that is sensitive to the concentration of oxygen. The phosphorescent compound is illuminated with short pulses of light, causing it to produce a phosphorescent emission having a rate of decay that varies as the function of the partial pressure of oxygen in the blood surrounding the phosphorescent compound. A detector produces an electrical signal corresponding to the intensity of the phosphorescent emission, and the electrical signal is converted to a corresponding digital value for input to a microcomputer. Also supplied to the microcomputer in digital form is a signal indicative of the temperature at the measurement site where the phosphorescent compound is disposed. The microcomputer determines the phosphorescent decay rate and from that value, determines the pO.sub.2 at the measurement site for the temperature at which the measurement was made. An initial estimate of a corresponding value for pO.sub.2 at the reference temperature is made as a function of the measurement temperature and the pO.sub.2 at that temperature.
Wolfbeis et al., U.S. Pat. No. 4,580,059, teaches the simultaneous measurement of the concentrations of several substances. A number of fluorescence measurements corresponding to the number of substances to be tested are performed using at least one fluorescent indicator which is non-specific relative to at least one of the substances to be tested. Each florescent indicator has different quenching constants with regard to the individual substances quenching its intensities. From the known, unquenched fluorescence intensities of the fluorescent indicators employed, the quenched fluorescence intensities obtained by measuring, and from the quenching constants that are known, or rather, have been determined beforehand by graphical methods or calculation, the concentrations and/or concentration ratios of the individual substances are obtained.
Clark, U.S. Pat. No. 4,401,122, discloses cutaneous methods for measuring substrates in mammalian subjects. A condition of the skin is used to measure a number of important substances which diffuse through the skin or are present underneath the skin in the blood or tissue. According to the technique, an enzyme whose activity is specific for a particular substance or substrate is placed on, in or under the skin for reaction. The condition of the skin is then detected by suitable means as a measure of the amount of the substrate in the body. For instance, the enzymatic reaction product or by-product of the reaction is detected directly through the skin as a measure of the amount of substrate. Polarographic electrodes or enzyme electrodes are employed as skin-contact analyzers in the transcutaneous measurement of oxygen or hydrogen peroxide to quantitatively detect substances such as glucose and alcohol. In a preferred quantitative technique, the skin is arterialized, i.e. heated or otherwise treated to arterialize the skin capillaries when the measurements are made. Colorimetric detection methods are also employed.
Among the various clinical measurements, the determination of blood gases (pH, pCO.sub.2, pO.sub.2) is one of the most important. Blood gases are routinely performed on patients in the Critical Care Unit. At present, such measurements are performed mostly by classical methods, such as gas chromatography and pH electrode, which are usually located in a central laboratory.
It is difficult to obtain the blood gas report in less than 30 minutes, by which time the patient's status is often quite different. Additionally, handling of blood by health-care workers is undesirable with regard to the risk of AIDS and other infectious diseases. At present, determination of blood gases is time-consuming and expensive, with a cost of at least $400,000,000 per year in the United States.
As can be seen by the above, there are a variety of techniques available for the measurement of blood gases and other substances. However a new apparatus and method are desired which can provide non-invasive continuous monitoring, immediate data availability, the ability to automatically save and transmit data for analysis, and can be used as part of a coordinated health monitoring system.